tbuckley/cabot-search huggingface dataset:
Telehealth weight loss program for breast cancer survivors is feasible and acceptable: Preliminary results of pilot clinical trial.
Authors: Julia C. Tchou
Journal: Journal of Clinical Oncology (2022)

TPS1603 Background: Current weight loss programs for breast cancer survivors utilize a hybrid of in-person visits or individualized telephone-based sessions modeled after the Diabetes Prevention Program. Telehealth may be an effective and efficient means of communicating with patients who otherwise cannot participate in in-person visits. To test this concept, we conducted a pilot single-arm study (NCT04855552) to examine the feasibility and acceptability of a weight loss group program via telehealth for breast cancer survivors. Methods: Patients &gt; = 18 years with ECOG performance 0 or 1, a BMI of ³ 25 kg/m 2 , and completion of adjuvant radio- and/or chemo-therapy &gt; 6 months were eligible. Patients attended weekly zoom teleconference counseling grouped sessions either at noon or 5 pm led by a licensed clinical psychologist for 20 weeks followed by sessions in weeks 22 and 24. Patients were encouraged to use MyFitnessPal.com, an online tool, to monitor calorie intake and physical activity and digital scales to monitor weight to share with study staff to enhance accountability and provide opportunity for feedback. Feasibility was defined as a ratio of enrolled/eligible patients ≥50%. Acceptability was assessed from surveys pre- and post-treatment, and qualitatively from exit interviews. Secondary endpoints included changes in Quality of Life-Breast Cancer Patient (QOF-BC), Patient Health Questionnaire (PHQ-9), and percent weight loss from baseline to 24 weeks. Results: Clinical characteristics of patients are summarized in Table. The ratio of enrolled (n = 12)/eligible (n = 23) participants was 52% thus confirming study feasibility. One patient dropped out after 2 sessions. Qualitative results from exit interviews showed that 7/9 patients rated the telehealth format as “extremely acceptable”. Surveys also indicated that the format and delivery of the program remained acceptable across most domains with no significant changes, except an increase in “approval” from 4.1 to 4.7 ( p= 0.05). Patients’ mood improved on the PHQ-9 from 4.2 to 1.2 (p = 0.03), and QOL-Physical Wellbeing improved from 56.9 to 66.3 (p = 0.004). Overall, 199 of 236 participant-sessions (84%) were attended. Percent weight loss was 6.5% +/- 2.5%. Conclusion: This proof-of-concept weight loss program was feasible and acceptable for our patients yielding improvements in QOL, mood, and a clinically significant weight loss over 6-months. This group-based video approach represents an intervention strategy that could be widely-disseminated and may provide stronger accountability/support than a one-on-one approach in some patients. Future work is aimed at refining strategies to increase patient enrollment/retention. Clinical trial information: NCT04855552. [Table: see text]
A fully automated MRI-based deep-learning algorithm for classifying germinomas and nongerminomatous germ cell tumors.
Authors: Yanong Li
Journal: Journal of Clinical Oncology (2022)

10035 Background: Intracranial germ cell tumors (iGCTs) are classified into two pathological subtypes (Germinomas [GEs] and nongerminomatous germ cell tumors [NGGCTs]), with distinct treatment strategies and prognosis. Accurate preoperative determination of iGCT subtypes is essential for clinical decision-making and prognosis assessment. We aim to develop and validate a deep-learning algorithm to automatically segment the iGCTs and classify their subtypes using preoperativeT2-weighted (T2W) images. Methods: Brain MR imaging and corresponding pathologic information were retrospectively obtained for 594 iGCTs, including 269 GEs and 325 NGGCTs from Beijing Tiantan Hospital (between January 1, 2008, and October 31, 2020). The retrospective set was subdivided into the training (n = 416) and test (n = 178) sets to develop and test a 3D nnU-Net using T2W images (here we named iGCT-net) for iGCT segmentation and its subtypes (GEs and NGGCTs) classification, simultaneously. A prospective cohort (n = 73, 56 GEs and 17 NGGCTs) was designed as a simulation set to test the model in a simulated clinical application. Dice scores were computed to assess tumor segmentation. Accuracy, sensitivity, specificity, and area under the curve (AUC) were used to assess the GEs and NGGCTs classification. Sensitivity analysis on subgroups with tumor locating at suprasellar, pineal, and basal ganglia in test and simulation set, respectively. Results: For tumor segmentation, the iGCT-net achieved a dice score of 0. 73 and 0.80 in test and simulation sets, respectively. For GEs and NGGCTs classification in the test set, the iGCT-net achieved an accuracy of 90.96%, sensitivity of 86.84% and specificity of 82.26%, and AUC of 84.87%. The iGCT-net showed 83.65% accuracy in the simulation set, with sensitivity of 83.56% and specificity of 83.72%, and AUC was 81.17%. In sensitivity analysis, the accuracies of the iGCT-net presented for the suprasellar region, pineal region, and basal ganglia region were 86.84%, 92.92%, and 61.73% in the test set, and 92.31%, 88.89%, and 72.27% for suprasellar region, pineal region, and basal ganglia region in the simulation set. Conclusions: We developed and validated a fully automatic deep learning algorithm to segment iGCT and classify GEs and NGGCTs with a high accuracy using only T2W images based on a large dataset.
CtDNA shed as a tool to select immune checkpoint inhibitors (ICPI) with or without chemotherapy for patients (pts) with advanced non–small cell lung cancer (aNSCLC).
Authors: Benjamin Besse, Russell Madison, Cheryl D. Cho-Phan, Jeremy Snider, Tamara Snow, Filippo Gustavo Dall'Olio, Khaled A. Tolba, Alexa Betzig Schrock, Geoffrey R. Oxnard
Journal: Journal of Clinical Oncology (2022)

9045 Background: ICPI are compelling therapies for pts with aNSCLC given the potential for durable benefit and limited toxicity. Even in tumors with biomarkers associated with ICPI response, early progression (eP) can be seen, leading to chemotherapy combination approaches. We hypothesize that ctDNA tumor fraction (TF) may identify pts at risk of eP on ICPI, helping to select the optimal first-line regimen. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database (FH-FMI CGDB). The de-identified data originated from ~280 US cancer clinics (~800 sites of care). Real-world overall survival (rwOS) accounting for delayed entry and real-world progression free survival (rwPFS) were estimated with Kaplan-Meier analysis. Hazard ratios (HR) were calculated using multivariate Cox proportional hazard models adjusting for relevant covariates. TF was calculated using an aneuploidy-based measure plus variant-based estimate and was categorized as follows: ≥10%: elevated, 1-10%: intermediate, &lt; 1%: low. eP was defined as rw progression within 8 weeks of starting therapy. Results: 426 pts with documented aNSCLC initiated 1st or 2nd line ICPI (128 ICPI, 298 ICPI+chemo) within 60 days of liquid biopsy. 88 (21%) pts had elevated TF, 193 (45%) had intermediate, and 145 (34%) had low. Pts with elevated TF had higher frequency of liver involvement (elevated: 27%; intermediate: 12%; low: 8%) and had worse performance status (ECOG 2+) near the start of therapy (elevated: 33%; intermediate 22%; low: 17%). PD-L1 was unknown for most pts (elevated: 44%; intermediate: 53%; low: 57%); elevated TF was associated with high PD-L1 positivity (elevated: 22%; intermediate: 17%; low: 12%). In pts with elevated TF, eP was more frequent (elevated: 26%, intermediate: 22%, low: 15%). Amongst all patients treated with either ICPI ± chemo, low TF was associated with better median rwPFS (low 6.7m [ref]; intermediate 5.1m, HR: 1.39 [1.11-1.74]; elevated 3.4m, HR: 1.74 [1.31-2.31]) and median rwOS: (low 14.2m [ref]; intermediate 8.4m, HR: 1.52 [1.10-2.09]; elevated 4.6m, HR: 2.17 [1.47-3.21]). In pts with elevated TF, the addition of chemo to ICPI was associated with favorable rwPFS and rwOS compared to pts who received ICPI alone (Table). Conclusions: ctDNA TF identifies pts with aNSCLC with an increased risk of eP on ICPI who may benefit from ICPI+chemo. In pts with low TF, outcomes on ICPI alone are favorable and similar to those receiving ICPI+chemo, suggesting low TF may be a non-invasive tool for identifying pts for single-agent ICPI. [Table: see text]
Characterization of alpelisib-associated hyperglycemia in metastatic breast cancer.
Authors: Sherry Shen, Yuan Chen, Andrea Carpio, Cassandra Chang, Neil M. Iyengar
Journal: Journal of Clinical Oncology (2022)

1016 Background: For women with metastatic hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer, the combination of alpelisib and fulvestrant improves progression-free survival in those with PIK3CA mutations. Hyperglycemia is a major toxicity of PI3K inhibitors including alpelisib, which limits the clinical efficacy of these drugs due to interrupted/reduced dosing and discontinuation. In the SOLAR-1 trial that led to the Food and Drug Administration (FDA) approval of alpelisib, over 60% of patients developed hyperglycemia of any grade, and over 36% developed grade 3-4 hyperglycemia. Here we describe the incidence and treatment of alpelisib-associated hyperglycemia in a single center cohort. Methods: Patients with metastatic breast cancer who received alpelisib on a clinical trial or as part of standard care from 2013-2021 at Memorial Sloan Kettering Cancer Center were included in this retrospective study. Patient and tumor characteristics and pre-treatment body mass index (BMI), hemoglobin A1c, and serum glucose levels were abstracted from medical records. Alpelisib dose interruptions, reductions, or discontinuation was recorded as well as endocrinology consultation and use of anti-hyperglycemic agents. Date of progression and/or death were recorded where applicable. Results: 247 patients were included in this study, among whom 245 (99.1%) were female and 198 (80.1%) were white. 100 (40.5%) were treated on a clinical trial. Median baseline BMI was 25.4 kg/m 2 . Among 164 patients with baseline hemoglobin A1c levels available, 93 (56.7%) patients had normal hemoglobin A1c, 54 (32.9%) had prediabetes, and 17 (10.4%) had diabetes. 152 patients (61.5%) developed hyperglycemia of any grade; 56 (22.7%) developed grade 3 and 16 (6.5%) developed grade 4 hyperglycemia. The median time to onset of hyperglycemia was 16 days. BMI ≥25 kg/m 2 or hemoglobin A1c ≥5.7% were strongly predictive of development of any-grade hyperglycemia ( p= 0.036 and p&lt; 0.001, respectively) and grade 3-4 hyperglycemia ( p&lt; 0.001 for both). Among those who developed hyperglycemia, 101 (40.9%) received treatment; 69 patients (27.9%) required only 1 anti-hyperglycemic agent whereas 9 (3.6%) required ≥3 anti-hyperglycemic agents. 49 (19.8%) were referred for endocrinology consult. In 66 patients (26.7%), alpelisib was held until resolution of hyperglycemia; 42 patients (17%) required dose reductions, and 11 (4.5%) discontinued alpelisib due to hyperglycemia. There was no significant difference in progression-free survival by hyperglycemia status or severity of hyperglycemia. Conclusions: Overweight BMI and hemoglobin A1c in the prediabetes or diabetes range were strongly predictive of developing alpelisib-associated hyperglycemia. Management of these co-morbidities prior to alpelisib treatment should be strongly considered.
Immunotherapy versus targeted therapy in the adjuvant setting for resected stage III melanoma: A single institution study.
Authors: Danai Dima, Nerea Lopetegui-Lia, Olisaemeka Ogbue, Bennett Osantowski, Ramsha Ahmed, Diana Basali, Fatimah Chamseddine, Donald Matthew Eicher, Jung Min Song, Brian Gastman, Lucy Boyce Kennedy, Pauline Funchain
Journal: Journal of Clinical Oncology (2022)

e21578 Background: Both immunotherapy (IO) and targeted therapy (TT) are approved as adjuvant (Adj) treatment for stage III melanoma, as they have proven to significantly decrease disease recurrence. While there is evidence to suggest overall survival (OS) benefit with TT, data demonstrating OS advantage with Adj IO is lacking. There are no prospective head-to-head trials to date comparing these two treatment modalities. Our aim is to determine whether Adj IO equally improves outcomes compared to Adj TT. Methods: We retrospectively analyzed 104 patients (pts) with resected stage III melanoma who received Adj IO or TT from 1/2016 - 12/2021. Relapse free survival (RFS), distant metastasis free survival (DMFS) and OS rates were assessed between the 2 groups. Results: Of 104 pts, 78 received IO (91% nivolumab, 7% pembrolizumab, 2% other) and 26 pts TT (100% dabrafenib/trametinib). Median follow up was 21 months. At data cutoff, among the 26 pts who received TT, 50% completed 1 year of planned therapy, whereas 50% discontinued TT prematurely (42% due to adverse events [AEs], 8% due to disease relapse). Among the 78 pts who received IO, 70% completed 1 year of planned treatment or continued to receive IO at the end of the study, whereas 30% discontinued IO prematurely (18% due to disease relapse, 12% due to AEs). Relapsed disease was noted in 6/26 (23%) and 27/78 (34.6%) pts of the TT and IO groups, respectively. With regards to location of recurrence, in the TT group 2/6 pts relapsed locally and 4/6 distally, whereas in the IO group 14/27 pts relapsed locally and 13/27 distally. The estimated median RFS of the TT vs IO groups was not reached (NA) (95% Cl: 17 months, NA) vs. 30 months (95% CI: 17 months, NA) respectively, which was not statistically significant (p = 0.49). Comparison of DMFS rate was found not to be statistically significant between the 2 groups (p = 0.86). Finally, median OS was NA in either group. At the end of the study 91% and 90.5% of the pts in the TT and IO arms, respectively, were still alive. The most common AEs in the TT group were fatigue (23%), fever (23%), nausea/vomiting (19%), whereas in the IO group were fatigue (22%), hypothyroidism (14%), diarrhea/colitis (10%), pruritic rash (9%). Conclusions: Both TT and IO appear to equally decrease disease recurrence, locally or distally, when given as Adj therapy for stage III melanoma. Prospective, randomized control trials with longer follow up and larger sample size are warranted to determine any difference in potential OS benefit.[Table: see text]
Do we need postoperative chemotherapy after preoperative FOLFIRINOX in resected borderline or locally advanced pancreatic cancer? A retrospective analysis.
Authors: Roxane Mari, Jonathan Garnier, Alexandra Lapeyre-Prost, Philippe Rochigneux, Yanis Dahel, Fabrice Caillol, Marc Giovannini, Olivier Turrini, Emmanuel Mitry, Brice Chanez
Journal: Journal of Clinical Oncology (2022)

4150 Background: Pancreatic ductal adenocarcinoma (PDAC) has poor outcome and surgical resection remains the only curative treatment. Post-operative (Post-Op) chemotherapy (CT) improves survival and FOLFIRINOX (FFX) regimen is the standard of care. Increasing number of patients with borderline resectable (BL) or locally advanced (LA) disease are treated with pre-operative (Pre-Op) CT with FFX. However, the benefit of Post-Op CT after Pre-Op FFX remains unclear. The aim of this study was to analyze the impact on survival of Post-Op CT in patients with resected BL or LA PDAC after Pre-Op FFX CT. Methods: 116 consecutive patients treated at the Institut Paoli-Calmettes comprehensive cancer center between 2014 and 2020 were retrospectively analyzed. All patients underwent pancreatectomy after Pre-Op FFX for a BL or LA PDAC. Patients who progressed or died within 3 months after surgery were excluded from the analysis. We compared median relapse-free survival (mRFS) and median overall survival (mOS) defined by time from surgery to relapse or death in patients who received or not Post-Op CT. Results: 116 patients (80% BL, 20% LA) were included: 82 received Post-Op CT (CT+) and 34 did not (CT-). The median number of Pre-Op FFX cycles was 4 in the CT+ group vs 6 in the CT- group. 24 (29.3%) patients received Post-Op FFX, 37 (45.1%) received Gemcitabine, 9 (11%) received Gemcitabine + Capecitabine, and 9 (11%) received a 5FU-based CT. Median time between surgery and first Post-Op CT cycle was 63 days. No difference in mRFS nor in mOS were found between CT+ and CT- groups: mRFS 15.0 vs 13.6 months, HR 1.1 [IC95% 0.69–1.77] and mOS 33.8 vs 36.1 months, HR 0.94 [IC95% 0.55–1.60]. Among patients with pathologic node positive disease (N+) (n = 79), mRFS was 13.9 months in the CT+ group vs 6.9 months in the CT- group (HR 0.68 [IC 0.35 – 1.19]), and mOS was 31.8 months in the CT+ group vs 16.5 months in the CT- group (HR 0.96 [IC95% 0.51-1.81]). Patients who received peri-operative (Peri-Op) FFX (n = 24) experienced longer mOS compared to patients who received Gemcitabine Post-Op CT: NR vs 33.8 months, HR 0.45 [IC95% 0.25-1.02]. Patients who received Peri-Op CT for a total of six months or more (n = 31) had increased mOS (55 vs 32 months, HR 0.61 [IC 95% 0.37- 1.11] and mRFS (16 vs 14 months HR 0.80, [IC95% 0.50 -1.31]) than patients receiving less than 6 months Peri-Op CT (n = 85) Conclusions: Post-Op CT does not clearly impact survival in BL or LA pancreatic cancer pretreated with Pre-Op FFX. We observed a trend in the N+ population for a survival benefit. Peri-Op FFX was associated with longer survival than Gemcitabine Post-Op regimen. Further randomized data are needed to assess the impact of Peri-Op FFX for these patients
Oncological outcomes of patients with non-clear cell renal cell cancers: Subtypes of unclassified and translocation renal cell cancers
Authors: F. Gökalp, S. Celik, T.S. Sozen, A.H. Ozen, G. Aslan, V. Izol, S. Baltaci, T. Muezzinoglu, B. Akdogan, E. Suer, I. Tinay
Journal: European Urology (2022)
Impaired humoral immunity is associated with prolonged COVID-19 despite robust CD8 T cell responses
Authors: Olga Lyudovyk, Justin Y. Kim, David Qualls, Madeline A. Hwee, Ya-Hui Lin, Sawsan R. Boutemine, Yuval Elhanati, Alexander Solovyov, Melanie Douglas, Eunise Chen, N. Esther Babady, Lakshmi Ramanathan, Pallavi Vedantam, Chaitanya Bandlamudi, Sigrid Gouma, Philip Wong, Scott E. Hensley, Benjamin Greenbaum, Alexander C. Huang, Santosha A. Vardhana
Journal: Cancer Cell (2022)
Label-free and automated approach to rapidly classify microsatellite instability (MSI) in early colon cancer (CC) analyzing the AIO ColoPredictPlus 2.0 (CPP) registry trial.
Authors: Stephanie Schörner, Frederik Großerueschkamp, Anna-Lena Kraeft, David Schuhmacher, Carlo Willy Sternemann, Inke Sabine Feder, Sarah Wisser, Celine Lugnier, Jens Christmann, Vera Heuer, Christian Teschendorf, Lothar Mueller, Axel Mosig, Dirk Arnold, Andrea Tannapfel, Klaus Gerwert, Anke C. Reinacher-Schick
Journal: Journal of Clinical Oncology (2022)

3616 Background: MSI due to mismatch repair defects accounts for 15-20% of all CC, has high prognostic and predictive value and is broadly utilized in treatment decisions. Artificial intelligence (AI) integrated, label-free quantum cascade laser (QCL) based infrared (IR) imaging resolves spatial and molecular alterations such as MSI in unstained cancer tissue sections. We aimed to evaluate the method for microsatellite instability/stability (MSI/MSS) classification in samples from the prospective multicenter AIO CPP registry trial. Methods: Paraffin-embedded unstained cancer tissue slides from patients (pts.) participating in CPP were measured (avg. 30 min/slide) and analyzed. The cohort was split into training (train), test (test), and validation (vali) sets. Cancer regions were first preselected based on a self-developed convolutional neural network (CNN) CompSegNet (Schuhmacher, medrxiv 2021). A VGG-16 CNN then classified MSI/MSS in these regions. Endpoints were area under receiver operating characteristic (AUROC) and area under precision recall curve (AUPRC). Results: 547 pts. (train n=331, test n=69, vali n=147) were analyzed. The baseline characteristics for the sub-cohorts are illustrated in the table. Mutation (MT) status: RAS MT: train 30% / test 30% / vali 37%; BRAF MT: train 27% / test 23% / vali 14%. The preselection of cancer regions reached a validation AUROC of 1.0. The subsequent MSI/MSS classifier reached a validation AUROC of 0.9 and AUPRC of 0.74 (sensitivity 85%, specificity 84%). Conclusions: Our multicenter approach using AI integrated label-free IR imaging provides an automated, fast, and reliable classification for MSI/MSS with an AUROC of 0.9 (sensitivity 85%, specificity 84%) almost comparable to the present gold standard immunohistochemistry. The method described here requires less samples for training when compared to other AI approaches which could facilitate the development of prognostic/predictive classifiers in the setting of randomized controlled trials. This novel technique may support further understanding of the increasingly important MSI CC cohort and support treatment decisions e.g. in specific subgroups such as targetable fusions. We expect our approach to be a broadly applicable diagnostic tool in the future.[Table: see text]